Clinical experience with antiinflammatory agents in patients with sepsis has been disappointing to date. We have found that several factors such as the site, type and severity of infection have important influences on many of these agents. Developing new agents which are impacted minimally by such factors, will increase the usefulness of this therapeutic approach. Oxidant injury is an important downstream event in the pathogenesis of sepsis. Targeting oxidants involved in this injury may be a more generally useful goal in sepsis. The enzyme superoxide dismutase (SOD) is an important regulator of oxidant injury. However, attempts to use recombinant SOD to limit inflammatory injury have been difficult because of its size and poor bioavailability. We are therefore now studying the influence of the factors listed above on the effects of a synthetic SOD mimetic agent which is small and has good bioavailability, in a rat model of sepsis.